The orthopedic device market has annual revenues in excess of a billion dollars in the United States alone. Biomedical companies produce orthopedic devices from polymeric and animal derived materials, such as DBM (demineralized bone matrix) powder and bone cement.
Such medical appliances are normally manufactured via chemical and thermal forming processes. Specifically, certain biological and polymeric materials are unable to withstand intense heat and their physical properties are significantly altered to a point where they are unstable, and in extreme cases, ultimately vaporize at elevated temperatures. Thus, when heat sensitive compounds are employed in the manufacture of medical devices, the use of heated molds, heated pourable forms and casts can be problematic.
Many medical devices, such as stents, catheters and endoscopes, are fabricated from, or coated with, sensitive polymers that cannot tolerate steam, irradiation, or ethylene oxide. Many new medical advances cannot be implemented because the sterilization industry is unable to provide a suitable sterilant as part of the manufacturing process. Plasma sterilization has been shown to be incompatible with some medical equipment and leaves toxic residues. Thus there is a need for a gentle and reliable sterilization method that results in greater than a 6-log reduction of microbial and viral contaminants in the material to be sterilized without deleteriously impacting the properties of the material being sterilized.
Recently, in U.S. Pat. No. 6,149,864 to Dillow et al. (the entire content of which is expressly incorporated hereinto by reference), the use of supercritical CO2 was disclosed as an alternative to existing technologies for sterilizing a wide range of products for the healthcare industry with little or no adverse effects on the material treated. Specifically, the Dillow '864 patent disclosed the inactivation of a wide range of vegetative microbial cells using supercritical carbon dioxide with agitation and pressure cycling. However, only one spore-forming bacterium was investigated in the Dillow '864 patent, specifically, B. cereus. No disclosure appears in Dillow et al. '864 patent regarding the efficacy of the therein suggested techniques using currently accepted bio-indicator standards used to judge sterilization (i.e., B. stearothermophilus and B. subtilis). Subsequently, however, other investigators achieved only a 3.5 log reduction in B. subtilis spores using the method disclosed in the Dillow et al. '864 patent.
Even more recently, in U.S. Pat. No. 7,108,832 to Christensen et al. (the entire content of which is expressly incorporated hereinto by reference), the use of supercritical CO2 was disclosed as an alternative to existing technologies for sterilizing a wide range of products for the healthcare industry with little or no adverse effects on the material treated.
Bacterial spores are more difficult to sterilize than vegetative cells. B. stearothermophilus and B. subtilis spores represent the greatest challenge to sterilization methods (FDA 1993) and are the currently accepted standards within the industry for validating sterilization methods. Sterilization is defined as greater than or equal to a 6-log (106) reduction in colony forming units (CFUs). Reproducible inactivation of these resistant microbes is required for commercialization of novel sterilization equipment and processes.
It would be highly desirable to develop a process for the manufacture of medical devices, such as implants, formed from green state materials utilizing a single step method resulting in the hardening of the material into a solid cast without exposure to the deleterious effects of heat. It would also be highly desirable to develop a process for the manufacture of medical devices, such as implants, formed from green state materials utilizing a single step method resulting in the simultaneous hardening and sterilization of the material into a solid cast. It is desirable to perform a simultaneous sterilization during the molding of the green materials to produce a formed medical device, such as an implant, that achieves a 6-log reduction in CFUs. The present invention is therefore directed to fulfilling such needs.